Research Projects

Aging and dementia imaging studies

Knight Alzheimer Research Imaging (KARI) Program

• • Knight Alzheimer Disease Research Center (ADRC) 

    • ADRC Center Grant, NIH/NIA P50AG005681

    • The Charles and Joanne Knight Alzheimer Disease Research Center Support Fund

    • The David and Betty Farrell Medical Research Fund

    • The Daniel J Brennan Alzheimer Research Fund

    • The Thomas E. Brew Foundation Fund

    • The Fred Simmons and Olga Mohan Alzheimer Research Support Fund

    • The Barnes-Jewish Hospital Foundation (BJHF)

    • The Willman Scholar Fund (BJHF)

QUANTIFICATION OF NEUROINFLAMMATION IN ALZHEIMER'S DISEASE USING DIFFUSION BASIS SPECTRUM IMAGING

• • • Funding:  1R01AG054567-01A1

    • Co-PI Yong Wang

    • Investigators

      • Qing Wang, Neuroimaging Laboratory

      • Nigel Cairns and Rick Perrin, Neuropathology

      • Jinbin Xu, Radiological Chemistry and Imaging Laboratory

      • Beau Ances, Neuroimaging Laboratory

    • Alzheimer disease (AD) is preceded by at least a decade of clinically silent brain changes (termed “preclinical AD”) that ultimately result in declines in memory and thinking. Inflammation in the brain may play an important role in the transition from normal cognition to dementia, but we lack easily accessible tools to identify neuroinflammation. The current application proposes to use a novel brain imaging test, diffusion basis spectrum imaging (DBSI), to examine inflammation during the stages of preclinical and clinical AD.

The Adult Children's Study (ACS)

• • • This is a longitudinal study of aging, beginning at age 45.  Imaging includes MRI, amyloid PIB-PET, and tau T807 PET. Early structural and functional changes in the brains of individuals at risk for developing dementia of the Alzheimer type (DAT) are not well understood. Typically a diagnosis of DAT is made using neuropsychological performance testing and clinical evaluation. Previous work by our group and others has identified a preclinical phase of DAT that is associated with a constellation of changes in biomarkers including decreased cerebral spinal fluid (CSF) Abeta42 (AP42) levels, increased fibrillar amyloid deposits in the brain as detected by PET 

    • Funding:

      • NIH/NIA P01AG026276

      • Generous support from Fred Simmons and Olga Mohan

      • Test-retest supported by ICTS-JIT = CTS ID#: JIT172M & MIR ID#: MIR11-022J

      • The McDonnell Center for Systems Neuroscience, 22 3922 26239N.

    • Collaborators Andrei Vlassenko and Marc Raichle are also performing [15]O and FDG metabolic PET in this cohort.

    • Collaborator David Balota has also performed task functional MRI in this cohort.

Healthy Aging and Senile Dementia (HASD)

• • • This is a longitudinal study of aging, beginning at age 65.  Imaging includes MRI, amyloid AV45-PET, and tau T807 (18F-AV-1451) PET.

    • Funding:  NIH/NIA P01AG003991 

      • Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly (florbetapir and AV1451 imaging).  For Florbetapir (AV45), Avid provided the doses and partial support for scanning through an investigator-initiated research grant awarded to Washington University (J.C. Morris, T.L.S. Benzinger).

      • Barnes-Jewish Hospital Foundation (PIB imaging)

      • Mallinckrodt Institute of Radiology (MRI in participants with dementia)

Tau PET imaging with AV-1451 (T807, flortaucipir)

• • • Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) provided technology transfer and provided precursor for AV-1451.

    • Hope Center for Neurological Disorders

    • Driving Performance in Preclinical AD, NIH R01AG043434

    • ADRC Project 1, NIH/NIA P50AG05681

    • HASD Project 4, NIH/NIA P01AG003991 

    • DIAN WU scans supported by the Barnes-Jewish Hospital Foundation and ICTS NIH/NCATS UL1TR000448

    • DIAN scans also supported by R01AG05255003 

    • ALS cohort supported by the McDonnell Center for Systems Neuroscience

    • FTD cohort supported by LEFTS

    • Posterior cortical atrophy cohort supported by the ICTS

    • HIV cohort supported by NIH R01NR014449

• International collaborations for Autosomal Dominant AD

  • Dominantly Inherited Alzheimer Network (DIAN) Imaging Core Lab

    • This is an international study of families with autosomal dominant AD.  Imaging includes MRI, amyloid PIB and AV45 PET, and tau T807 PET.

    • Funding

      • NIH/NIA UF1AG032438, NIH/NIA U19AG03243808  and the German Center for Neurodegenerative Diseases (DZNE)

      • NIH/NIA R01AG052550-01A1 for Tau PET in DIAN, and imaging-pathology correlation studies 

  • Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) Imaging Core Lab

    • This is an international study of families with autosomal dominant AD.  Imaging includes MRI, amyloid PIB and AV45 PET, and tau T807 (AV-1451) PET.

    • Funding

      • NIA/NINDA U01AG042791-02 Phase II

      • NIH/NIA R01AG046179 Phase III

      • DIAN Trials Pharma Consortium

      • Avid Radiopharmaceuticals, Lilly, Roche, MNI

Brain tumor imaging studies 

• • Neurosurgical Translational Interface Pipeline for Clinical Resting State Functional MRI

    • Barnes-Jewish Hospital Foundation, 8000-88

  • The goal of this project is to develop a clinical workflow for volumetric MRI and resting state functional MRI for preoperative planning and for evaluation of dementia.

Additional sources of funding

• Willman Scholar, The Foundation for Barnes-Jewish Hospital (supports Austin McCullough and Brian Gordon's work in AD Research)

• Support for image acquisition - CCIR/ICTS Human Imaging Unit.  NIH/NCATS UL1TR000448

• CCIR additionally supported for Vision OET/CT: "This work was supported by NIH grant S10OD025214 for the Vision PET/CT Scanner housed in the Center for Clinical Imaging Research (CCIR), Mallinckrodt Institute of Radiology, Washington University in St. Louis.” 

• Support for imaging informatics - CNDA/XNAT "This study was supported in part by the Neuroimaging Informatics and Analysis Center (1P30NS098577) and R01 EB009352."

Studies closed to enrollment

• • Pediatric white matter disease

    • National Multiple Sclerosis Society RG 419A2

  • FDOPA-PET/MRI for the Pre-operative Evaluation of Glioma

    • Washington University Institute of Clinical and Translational Sciences grant UL1TR000448 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH), CONDR R01NS066905

    • Barnes-Jewish Hospital Foundation / Siteman Cancer Center

Additional conflicts of interest:  Dr. Benzinger has currently or has previously recieved investigator initiated research funding from the NIH, the Alzheimer's Association, the Barnes-Jewish Hospital Foundation, Siemens Healthineers and Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) Dr. Benzinger participates as a site investigator in clinical trials sponsored by Avid Radiopharmaceuticals, Eli Lilly, Biogen, Eisai, Jaansen, and Roche.  Dr. Benzinger performs paid and unpaid consulting  for Biogen, Eli Lilly, Eisai, Jaansen and Siemens.

List of our open clinical trials:  https://clinicaltrials.gov/ct2/results?term=benzinger&pg=1